Haemophilus influenzae (H. influenzae) is a gram-negative, facultative aerobe that colonizes the respiratory tract of humans, the only natural host known for this bacterium. It is a common cause of otitis media, upper and lower respiratory tract infections, septicemia, and meningitis in children. During the course of infection, H. influenzae is likely to encounter varying environmental conditions such as the relatively high oxygen environment of the airway surface to sites lower in oxygen such as an interstitial location during traversal of the mucosal epithelium, entry into bloodstream, or spread to the middle ear.
Putative genes known to play a role in bacterial pathogenesis may include sodA (superoxide dismutase), lctP (L-lactate permease), and lpdA (dihydrolipoamide dehydrogenase), whose respective homologues in E. coli have been shown to be responsive to redox conditions. Compan et al. (1993); Lynch et al. (1996); and Cunningham et al. (1998). In infant rat models of H. influenzae infection, sodA was shown to be important for oxidative stress defense and for optimal nasopharyngeal colonization. D'Mello et al. (1997). Another enzyme, lctP, is required for H. influenzae survival in the bloodstream. Herbert et al. (2002). Further, lpdA, a component of the pyruvate and a-ketoglutarate dehydrogenases, is needed for aerobic growth in vitro and for bacteremia. Herbert et al. (2003).
H. influenzae virulence may result from gene expression modulation in response to environmental redox growth conditions as it transits between microenvironments within the host. What is needed are compositions and methods to reduce or eliminate the genetically directed colonization and pathogenesis of H. influenzae without affecting host cells.